case study on schizophrenia pdf

Module 11: Schizophrenia Spectrum and Other Psychotic Disorders

Case studies: schizophrenia spectrum disorders, learning objectives.

• Identify schizophrenia and psychotic disorders in case studies

Case Study: Bryant

Thirty-five-year-old Bryant was admitted to the hospital because of ritualistic behaviors, depression, and distrust. At the time of admission, prominent ritualistic behaviors and depression misled clinicians to diagnose Bryant with obsessive-compulsive disorder (OCD). Shortly after, psychotic symptoms such as disorganized thoughts and delusion of control were noticeable. He told the doctors he has not been receiving any treatment, was not on any substance or medication, and has been experiencing these symptoms for about two weeks. Throughout the course of his treatment, the doctors noticed that he developed a catatonic stupor and a respiratory infection, which was identified by respiratory symptoms, blood tests, and a chest X-ray. To treat the psychotic symptoms, catatonic stupor, and respiratory infection, risperidone, MECT, and ceftriaxone (antibiotic) were administered, and these therapies proved to be dramatically effective. [1]

Case Study: Shanta

Shanta, a 28-year-old female with no prior psychiatric hospitalizations, was sent to the local emergency room after her parents called 911; they were concerned that their daughter had become uncharacteristically irritable and paranoid. The family observed that she had stopped interacting with them and had been spending long periods of time alone in her bedroom. For over a month, she had not attended school at the local community college. Her parents finally made the decision to call the police when she started to threaten them with a knife, and the police took her to the local emergency room for a crisis evaluation.

Following the administration of the medication, she tried to escape from the emergency room, contending that the hospital staff was planning to kill her. She eventually slept and when she awoke, she told the crisis worker that she had been diagnosed with attention-deficit/hyperactive disorder (ADHD) a month ago. At the time of this ADHD diagnosis, she was started on 30 mg of a stimulant to be taken every morning in order to help her focus and become less stressed over the possibility of poor school performance.

After two weeks, the provider increased her dosage to 60 mg every morning and also started her on dextroamphetamine sulfate tablets (10 mg) that she took daily in the afternoon in order to improve her concentration and ability to study. Shanta claimed that she might have taken up to three dextroamphetamine sulfate tablets over the past three days because she was worried about falling asleep and being unable to adequately prepare for an examination.

Prior to the ADHD diagnosis, the patient had no known psychiatric or substance abuse history. The urine toxicology screen taken upon admission to the emergency department was positive only for amphetamines. There was no family history of psychotic or mood disorders, and she didn’t exhibit any depressive, manic, or hypomanic symptoms.

The stimulant medications were discontinued by the hospital upon admission to the emergency department and the patient was treated with an atypical antipsychotic. She tolerated the medications well, started psychotherapy sessions, and was released five days later. On the day of discharge, there were no delusions or hallucinations reported. She was referred to the local mental health center for aftercare follow-up with a psychiatrist. [2]

Another powerful case study example is that of Elyn R. Saks, the associate dean and Orrin B. Evans professor of law, psychology, and psychiatry and the behavioral sciences at the University of Southern California Gould Law School.

Saks began experiencing symptoms of mental illness at eight years old, but she had her first full-blown episode when studying as a Marshall scholar at Oxford University. Another breakdown happened while Saks was a student at Yale Law School, after which she “ended up forcibly restrained and forced to take anti-psychotic medication.” Her scholarly efforts thus include taking a careful look at the destructive impact force and coercion can have on the lives of people with psychiatric illnesses, whether during treatment or perhaps in interactions with police; the Saks Institute, for example, co-hosted a conference examining the urgent problem of how to address excessive use of force in encounters between law enforcement and individuals with mental health challenges.

Saks lives with schizophrenia and has written and spoken about her experiences. She says, “There’s a tremendous need to implode the myths of mental illness, to put a face on it, to show people that a diagnosis does not have to lead to a painful and oblique life.”

In recent years, researchers have begun talking about mental health care in the same way addiction specialists speak of recovery—the lifelong journey of self-treatment and discipline that guides substance abuse programs. The idea remains controversial: managing a severe mental illness is more complicated than simply avoiding certain behaviors. Approaches include “medication (usually), therapy (often), a measure of good luck (always)—and, most of all, the inner strength to manage one’s demons, if not banish them. That strength can come from any number of places…love, forgiveness, faith in God, a lifelong friendship.” Saks says, “We who struggle with these disorders can lead full, happy, productive lives, if we have the right resources.”

You can view the transcript for “A tale of mental illness | Elyn Saks” here (opens in new window) .

• Bai, Y., Yang, X., Zeng, Z., & Yang, H. (2018). A case report of schizoaffective disorder with ritualistic behaviors and catatonic stupor: successful treatment by risperidone and modified electroconvulsive therapy. BMC psychiatry , 18(1), 67. https://doi.org/10.1186/s12888-018-1655-5 ↵
• Henning A, Kurtom M, Espiridion E D (February 23, 2019) A Case Study of Acute Stimulant-induced Psychosis. Cureus 11(2): e4126. doi:10.7759/cureus.4126 ↵
• Modification, adaptation, and original content. Authored by : Wallis Back for Lumen Learning. Provided by : Lumen Learning. License : CC BY: Attribution
• A tale of mental illness . Authored by : Elyn Saks. Provided by : TED. Located at : https://www.youtube.com/watch?v=f6CILJA110Y . License : Other . License Terms : Standard YouTube License
• A Case Study of Acute Stimulant-induced Psychosis. Authored by : Ashley Henning, Muhannad Kurtom, Eduardo D. Espiridion. Provided by : Cureus. Located at : https://www.cureus.com/articles/17024-a-case-study-of-acute-stimulant-induced-psychosis#article-disclosures-acknowledgements . License : CC BY: Attribution
• Elyn Saks. Provided by : Wikipedia. Located at : https://en.wikipedia.org/wiki/Elyn_Saks . License : CC BY-SA: Attribution-ShareAlike
• A case report of schizoaffective disorder with ritualistic behaviors and catatonic stupor: successful treatment by risperidone and modified electroconvulsive therapy. Authored by : Yuanhan Bai, Xi Yang, Zhiqiang Zeng, and Haichen Yangcorresponding. Located at : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5851085/ . License : CC BY: Attribution

Schizophrenia case studies: putting theory into practice

This article considers how patients with schizophrenia should be managed when their condition or treatment changes.

DR P. MARAZZI/SCIENCE PHOTO LIBRARY

Treatments for schizophrenia are typically recommended by a mental health specialist; however, it is important that pharmacists recognise their role in the management and monitoring of this condition. In ‘ Schizophrenia: recognition and management ’, advice was provided that would help with identifying symptoms of the condition, and determining and monitoring treatment. In this article, hospital and community pharmacy-based case studies provide further context for the management of patients with schizophrenia who have concurrent conditions or factors that could impact their treatment.

Case study 1: A man who suddenly stops smoking

A man aged 35 years* has been admitted to a ward following a serious injury. He has been taking olanzapine 20mg at night for the past three years to treat his schizophrenia, without any problems, and does not take any other medicines. He smokes 25–30 cigarettes per day, but, because of his injury, he is unable to go outside and has opted to be started on nicotine replacement therapy (NRT) in the form of a patch.

When speaking to him about his medicines, he appears very drowsy and is barely able to speak. After checking his notes, it is found that the nurses are withholding his morphine because he appears over-sedated. The doctor asks the pharmacist if any of the patient’s prescribed therapies could be causing these symptoms.

What could be the cause?

Smoking is known to increase the metabolism of several antipsychotics, including olanzapine, haloperidol and clozapine. This increase is linked to a chemical found in cigarettes, but not nicotine itself. Tobacco smoke contains aromatic hydrocarbons that are inducers of CYP1A2, which are involved in the metabolism of several medicines [1] , [2] , [3] . Therefore, smoking cessation and starting NRT leads to a reduction in clearance of the patient’s olanzapine, leading to increased plasma levels of the antipsychotic olanzapine and potentially more adverse effects — sedation in this case.

Patients who want to stop, or who inadvertently stop, smoking while taking antipsychotics should be monitored for signs of increased adverse effects (e.g. extrapyramidal side effects, weight gain or confusion). Patients who take clozapine and who wish to stop smoking should be referred to their mental health team for review as clozapine levels can increase significantly when smoking is stopped [3] , [4] .

For this patient, olanzapine is reduced to 15mg at night; consequently, he seems much brighter and more responsive. After a period on the ward, he has successfully been treated for his injury and is ready to go home. The doctor has asked for him to be supplied with olanzapine 15mg for discharge along with his NRT.

What should be considered prior to discharge?

It is important to discuss with the patient why his dose was changed during his stay in hospital and to ask whether he intends to start smoking again or to continue with his NRT. Explain to him that if he wants to begin, or is at risk of, smoking again, his olanzapine levels may be impacted and he may be at risk of becoming unwell. It is necessary to warn him of the risk to his current therapy and to speak to his pharmacist or mental health team if he does decide to start smoking again. In addition, this should be used as an opportunity to reinforce the general risks of smoking to the patient and to encourage him to remain smoke-free.

It is also important to speak to the patient’s community team (e.g. doctors, nurses), who specialise in caring for patients with mental health disorders, about why the olanzapine dose was reduced during his stay, so that they can then monitor him in case he does begin smoking again.

Case 2: A woman with constipation

A woman aged 40 years* presents at the pharmacy. The pharmacist recognises her as she often comes in to collect medicine for her family. They are aware that she has a history of schizophrenia and that she was started on clozapine three months ago. She receives this from her mental health team on a weekly basis.

She has visited the pharmacy to discuss constipation that she is experiencing. She has noticed that since she was started on clozapine, her bowel movements have become less frequent. She is concerned as she is currently only able to go to the toilet about once per week. She explains that she feels uncomfortable and sick, and although she has been trying to change her diet to include more fibre, it does not seem to be helping. The patient asks for advice on a suitable laxative.

What needs to be considered?

Constipation is a very common side effect of clozapine . However, it has the potential to become serious and, in rare cases, even fatal [5] , [6] , [7] , [8] . While minor constipation can be managed using over-the-counter medicines (e.g. stimulant laxatives, such as senna, are normally recommended first-line with stool softeners, such as docusate, or osmotic laxatives, such as lactulose, as an alternative choice), severe constipation should be checked by a doctor to ensure there is no serious bowel obstruction as this can lead to paralytic ileus, which can be fatal [9] . Symptoms indicative of severe constipation include: no improvement or bowel movement following laxative use, fever, stomach pain, vomiting, loss of appetite and/or diarrhoea, which can be a sign of faecal impaction overflow.

As the patient has been experiencing this for some time and is only opening her bowels once per week, as well as having other symptoms (i.e. feeling uncomfortable and sick), she should be advised to see her GP as soon as possible.

The patient returns to the pharmacy again a few weeks later to collect a prescription for a member of their family and thanks the pharmacist for their advice. The patient was prescribed a laxative that has led to resolution of symptoms and she explains that she is feeling much better. Although she has a repeat prescription for lactulose 15ml twice per day, she says she is not sure whether she needs to continue to take it as she feels better.

What advice should be provided?

As she has already had an episode of constipation, despite dietary changes, it would be best for the patient to continue with the lactulose at the same dose (i.e. 15ml twice daily), to prevent the problem occurring again. Explain to the patient that as constipation is a common side effect of clozapine, it is reasonable for her to take laxatives before she gets constipation to prevent complications.

Pharmacists should encourage any patient who has previously had constipation to continue taking prescribed laxatives and explain why this is important. Pharmacists should also continue to ask patients about their bowel habits to help pick up any constipation that may be returning. Where pharmacists identify patients who have had problems with constipation prior to starting clozapine, they can recommend the use of a prophylactic laxative such as lactulose.

Case 3: A mother is concerned for her son who is talking to someone who is not there

A woman has been visiting the pharmacy for the past 3 months to collect a prescription for her son, aged 17 years*. In the past, the patient has collected his own medicine. Today the patient has presented with his mother; he looks dishevelled, preoccupied and does not speak to anyone in the pharmacy.

His mother beckons you to the side and expresses her concern for her son, explaining that she often hears him talking to someone who is not there. She adds that he is spending a lot of time in his room by himself and has accused her of tampering with his things. She is not sure what she should do and asks for advice.

What action can the pharmacist take?

It is important to reassure the mother that there is help available to review her son and identify if there are any problems that he is experiencing, but explain it is difficult to say at this point what he may be experiencing. Schizophrenia is a psychotic illness which has several symptoms that are classified as positive (e.g. hallucinations and delusions), negative (e.g. social withdrawal, self-neglect) and cognitive (e.g. poor memory and attention).

Many patients who go on to be diagnosed with schizophrenia will experience a prodromal period before schizophrenia is diagnosed. This may be a period where negative symptoms dominate and patients may become isolated and withdrawn. These symptoms can be confused with depression, particularly in younger people, though depression and anxiety disorders themselves may be prominent and treatment for these may also be needed. In this case, the patient’s mother is describing potential psychotic symptoms and it would be best for her son to be assessed. She should be encouraged to take her son to the GP for an assessment; however, if she is unable to do so, she can talk to the GP herself. It is usually the role of the doctor to refer patients for an assessment and to ensure that any other medical problems are assessed. 

Three months later, the patient comes into the pharmacy and seems to be much more like his usual self, having been started on an antipsychotic. He collects his prescription for risperidone and mentions that he is very worried about his weight, which has increased since he started taking the newly prescribed tablets. Although he does not keep track of his weight, he has noticed a physical change and that some of his clothes no longer fit him.

What advice can the pharmacist provide?

Weight gain is common with many antipsychotics [10] . Risperidone is usually associated with a moderate chance of weight gain, which can occur early on in treatment [6] , [11] , [12] . As such, the National Institute for Health and Care Excellence recommends weekly monitoring of weight initially [13] . As well as weight gain, risperidone can be associated with an increased risk of diabetes and dyslipidaemia, which must also be monitored [6] , [11] , [12] . For example, the lipid profile and glucose should be assessed at 12 weeks, 6 months and then annually [12] .

The pharmacist should encourage the patient to attend any appointments for monitoring, which may be provided by his GP or mental health team, and to speak to his mental health team about his weight gain. If he agrees, the pharmacist could inform the patient’s mental health team of his weight gain and concerns on his behalf. It is important to tackle weight gain early on in treatment, as weight loss can be difficult to achieve, even if the medicine is changed.

The pharmacist should provide the patient with advice on healthy eating (e.g. eating a balanced diet with at least five fruit and vegetables per day) and exercising regularly (e.g. doing at least 150 minutes of moderate-intensity activity or 75 minutes of vigorous-intensity activity per week), and direct him to locally available services. The pharmacist can record the adverse effect on the patient’s medical record, which will help flag this in the future and thus help other pharmacists to intervene should he be prescribed risperidone again.

*All case studies are fictional.

Useful resources

• Mind — Schizophrenia
• Rethink Mental Illness — Schizophrenia
• Mental Health Foundation — Schizophrenia
• Royal College of Psychiatrists — Schizophrenia
• NICE guidance [CG178] — Psychosis and schizophrenia in adults: prevention and management
• NICE guidance [CG155] — Psychosis and schizophrenia in children and young people: recognition and management
• British Association for Psychopharmacology — Evidence-based guidelines for the pharmacological treatment of schizophrenia: updated recommendations from the British Association for Psychopharmacology

About the author

Nicola Greenhalgh is lead pharmacist, Mental Health Services, North East London NHS Foundation Trust

[1] Chiu CC, Lu ML, Huang MC & Chen KP. Heavy smoking, reduced olanzapine levels, and treatment effects: a case report. Ther Drug Monit 2004;26(5):579–581. doi: 10.1097/00007691-200410000-00018

[2] de Leon J. Psychopharmacology: atypical antipsychotic dosing: the effect of smoking and caffeine. Psychiatr Serv 2004;55(5):491–493. doi: 10.1176/appi.ps.55.5.491

[3] Mayerova M, Ustohal L, Jarkovsky J et al . Influence of dose, gender, and cigarette smoking on clozapine plasma concentrations. Neuropsychiatr Dis Treat 2018;14:1535–1543. doi: 10.2147/NDT.S163839

[4] Ashir M & Petterson L. Smoking bans and clozapine levels. Adv Psychiatr Treat 2008;14(5):398–399. doi: 10.1192/apt.14.5.398b

[5] Young CR, Bowers MB & Mazure CM. Management of the adverse effects of clozapine. Schizophr Bull 1998;24(3):381–390. doi: 10.1093/oxfordjournals.schbul.a033333

[6] Taylor D, Barnes TRE & Young AH. The Maudsley Prescribing Guidelines in Psychiatry . 13th edn. London: Wiley Blackwell; 2018

[7] Oke V, Schmidt F, Bhattarai B et al . Unrecognized clozapine-related constipation leading to fatal intra-abdominal sepsis — a case report. Int Med Case Rep J 2015;8:189–192. doi: 10.2147/IMCRJ.S86716

[8] Hibbard KR, Propst A, Frank DE & Wyse J. Fatalities associated with clozapine-related constipation and bowel obstruction: a literature review and two case reports. Psychosomatics 2009;50(4):416–419. doi: 10.1176/appi.psy.50.4.416

[9] Medicines and Healthcare products Regulatory Agency. Clozapine: reminder of potentially fatal risk of intestinal obstruction, faecal impaction, and paralytic ileus. 2020. Available from: https://www.gov.uk/drug-safety-update/clozapine-reminder-of-potentially-fatal-risk-of-intestinal-obstruction-faecal-impaction-and-paralytic-ileus (accessed April 2020)

[10] Leucht S, Cipriani A, Spineli L et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 2013;382(9896):951–962. doi: 10.1016/S0140-6736(13)60733-3

[11] Bazire S. Psychotropic Drug Directory . Norwich: Lloyd-Reinhold Communications LLP; 2018

[12] Cooper SJ & Reynolds GP. BAP guidelines on the management of weight gain, metabolic disturbances and cardiovascular risk associated with psychosis and antipsychotic drug treatment. J Psychopharmacol 2016;30(8):717–748. doi: 10.1177/0269881116645254

[13] National Institute for Health and Care Excellence. Psychosis and schizophrenia in adults: prevention and management. Clinical guideline [CG178]. 2014. Available from: https://www.nice.org.uk/guidance/cg178 (accessed April 2020)

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CASE REPORT article

Early-onset schizophrenia with predominantly negative symptoms: a case study of a drug-naive female patient treated with cariprazine.

• Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, Hungary

Schizophrenia is a chronic and severe mental disorder characterized by positive, negative, and cognitive symptoms. Negative symptoms are usually present from the prodromal phase; early diagnosis and management of negative symptoms is a major health concern since an insidious onset dominated by negative symptoms is associated with a worse outcome. Antipsychotic medications, which are effective for treating positive symptoms, are generally ineffective for treating negative or cognitive symptoms. We present a 23-year-old woman showing severe symptoms at her first visit to our department. The patient’s parents reported that their daughter had experienced several years of psychosocial decline and putative psychiatric symptoms, but no medical attention had been previously sought; as such, the diagnosis of schizophrenia with predominantly negative symptoms was very much delayed. Early onset of schizophrenia, longer duration of untreated psychosis, and severe negative symptoms, which have limited treatment options, suggested a poor prognosis. We initiated monotherapy with cariprazine, a novel antipsychotic that has recently been proven efficacious in treating schizophrenia with predominantly negative symptoms. This report describes a 52-week cariprazine treatment regimen and follows the patient’s impressive clinical improvement confirmed by PANSS and CGI scores, and psychological tests.

Schizophrenia is a severe, chronic, and heterogeneous mental disorder that often has debilitating long-term outcomes. Its lifetime prevalence rate is estimated to be approximately 1% worldwide in the adult population ( Lehman et al., 2010 ). Onset generally occurs in late adolescence or early adulthood, with an average age of 18 years for men and 25 years for women. 1 The term early-onset schizophrenia (EOS) is used to refer to patients who are diagnosed with the disorder before this age. EOS is a severe, frequently disabling, and chronic condition with a prevalence approaching 0.5% in those younger than 18 years ( Hafner and Van der Heiden, 1997 ).

Schizophrenia is accompanied by a distortion of personality that affects fundamental mental and social functions, making everyday life extremely difficult for patients. Clinical symptoms are often classified in three main domains: positive symptoms, such as hallucinations, delusions, suspiciousness/persecution; negative symptoms, such as emotional withdrawal, blunted affect, and passive social withdrawal; and cognitive symptoms, such as impaired perception, learning, thinking, and memorizing. EOS may be accompanied by greater symptom severity, premorbid developmental impairment, ‘soft’ neurological signs (eg, clumsiness, motor incoordination), and a higher rate of substance abuse ( Hsiao and McClellan, 2008 ; Clemmensen et al., 2012 ; Immonen et al., 2017 ). Accordingly, diagnosis of EOS is often difficult and frequently delayed since onset is more commonly insidious than acute, which makes it difficult to differentiate EOS from underlying cognitive deficits, premorbid functional impairment, or other abnormalities ( Russell, 1994 ; Bartlet, 2014 ). Given this common delay in recognition of the disorder, the duration of untreated psychosis is often very long, further contributing to a poor outcome ( Penttila et al., 2014 ).

Although various hypotheses have been developed, the etiopathogenesis of schizophrenia and EOS is not fully understood ( McGuffin, 2004 ; Klosterkotter et al., 2011 ). 2 Among the rising and falling neurochemical theories, the dopamine hypothesis has remained a primary hypothesis guiding the treatment of schizophrenia. There are four dopaminergic pathways in the human brain: the mesolimbic, the mesocortical, the tuberoinfundibular, and the nigrostriatal. Positive symptoms of schizophrenia are associated with the hyperdopaminergic state of D 2 receptors in the mesolimbic area, while negative and cognitive symptoms are believed to be related to the hypodopaminergic dysregulation of the prefrontal cortex ( Stahl, 2003 ).

Negative symptoms of schizophrenia, which affect up to 60% of patients with schizophrenia ( Rabinowitz et al., 2013 ), form a complex clinical constellation of symptoms that challenge both diagnosis and treatment. By definition, negative symptoms mean the absence of normal functions. Negative symptoms are classified by their etiology as primary negative symptoms, which are core features of the disease itself, and secondary negative symptoms, which are consequences of positive symptoms, antipsychotic treatment, depression or extrapyramidal side effects. Five constructs have been accepted by general consensus as key aspects of negative symptoms: blunted affect, alogia, anhedonia, asociality, and avolition ( Marder and Galderisi, 2017 ). Patients with predominant negative symptoms lose their motivation, cannot function at school or work, and their interpersonal relationships severely decay. Due to impaired daily functioning and social amotivation, they may need constant care.

Although early intervention is associated with improvement in negative symptoms ( Boonstra et al., 2012 ), this may be challenging since negative symptoms develop slowly and may be difficult to detect or differentiate from other clinical features ( Kirkpatrick et al., 2001 ; Galderisi et al., 2018 ). Moreover, a more insidious onset predicts poorer outcome and more severe negative symptoms ( Kao and Liu, 2010 ; Immonen et al., 2017 ; Murru and Carpiniello, 2018 ). Diagnosis of patients with predominantly negative symptoms (lacking manifest psychotic signs) is often delayed, resulting in a longer duration of untreated psychosis. The length of untreated psychosis is closely related to poorer functional outcome ( Perkins et al., 2005 ).

Negative symptoms have traditionally had minimal response to antipsychotic treatment. First-generation antipsychotics are effective in treating positive symptoms, but negative symptom improvement is only evident when symptoms are secondary to positive symptoms. It was initially hoped that second-generation antipsychotics would target both positive and negative symptoms, but efficacy data have been disappointing. This was a large meta-analysis where only four second-generation drugs (amisulpride, risperidone, olanzapine, and clozapine) resulted to be more efficacious than first-generation antipsychotics in the overall change of symptoms, including positive and negative symptoms. The other examined second-generation antipsychotics were only as efficacious as first-generation antipsychotic agents ( Leucht et al., 2009 ). These studies were mainly conducted in patients with general symptoms of schizophrenia, therefore a secondary effect on negative symptoms could not be ruled out. Therefore negative symptom improvement cannot be considered a core component of atypicality ( Veerman et al., 2017 ). Previous studies have demonstrated that no drug had a beneficial effect on negative symptoms when compared to another drug ( Arango et al., 2013 ; Millan et al., 2014 ; Fusar-Poli et al., 2015 ), meaning that head to head comparisons of different agents among each other did not result in superiority of one drug to another. The latest comparison ( Krause et al., 2018 ) evaluated all studies that have been performed in the negative symptom population so far, and has found that amisulpride claimed superiority only to placebo, olanzapine was superior to haloperidol, but only in a small trial (n = 35), and cariprazine outperformed risperidone in a large well-controlled trial.

Hence cariprazine emerged as an agent of particular interest in regard to negative symptoms. Cariprazine is a dopamine D 3 /D 2 receptor partial agonist and serotonin 5-HT 1A receptor partial agonist. It has been hypothesized that cariprazine is the only antipsychotic that can block D 3 receptors in the living brain, thereby exhibiting functions that are related to D 3 blockade (e.g., improvement of negative symptoms) ( Stahl, 2016 ). In that large clinical trial including 460 patients with predominant negative symptoms and stable positive symptoms of schizophrenia, cariprazine was significantly more effective than risperidone in improving negative symptoms and patient functioning ( Nemeth et al., 2017 ).

Case Description

The 23-year-old female patient visited the Institute of Rare Diseases at our university with her parents. They had suspected for a long time that something was wrong with their daughter, but this was the first time they had asked for medical help. The patient was quiet and restrained since she did not speak much, her parents told us her story instead. Initially, the patient had done very well in a bilingual secondary school and was socially active with friends and peers. At the age of 15 years, her academic performance started to deteriorate, with her first problems associated with difficulty learning languages and memorizing. Her school grades dropped, and her personality started to gradually change. She became increasingly irritated, and was verbally and physically hostile toward her classmates, resorting to hitting and kicking at times. She was required to repeat a school year and subsequently dropped out of school at the age of 18 because she was unable to complete her studies. During these years, her social activity greatly diminished. She lived at home with her parents, did not go out with friends, or participate in relationships. Most of the time she was silent and unsociable, but occasionally she had fits of laughter without reason. Once the patient told her mother that she could hear the thoughts of others and was probably hearing voices as well. Slowly, her impulse-control problems faded; however, restlessness of the legs was quite often present.

Our patient’s medical history was generally unremarkable. She lacked neurological or psychiatric signs. She had a tonsillectomy and adenotomy at age 7 years. Epilepsy was identified in the patient’s family history (father’s uncle). On physical examination, there were no signs of internal or neurological disease; body mass index was 21.5 (normal weight).

During the first psychiatric interview and examination, we found that our patient was alert and vigilant, but had trouble relating due to decreased integrity of consciousness. Her attention could be aroused or partially directed, and she had difficulty keeping a target idea. Autopsychic and allopsychic orientations were preserved. Longer thinking latencies and slowed movement responses were observed, sometimes with even cataleptic impressions. Cognitive functions, such as thinking, memory, and concept formation, were severely impaired, and we were unable to carry out some of our neurocognitive tests -such as the Addenbrooke’s Cognitive Examination ( Hsieh et al., 2013 ), the Toulouse-Pieron attention test (Kanizsa G1951), Bells test ( Gauthier et al., 1989 ) and the Trail Making Test- because of the patient’s denial of symptoms and refusal to cooperate.

She often looked aside and laughed frequently, suggesting the presence of perceptual disturbances, but she denied her symptoms when asked. In contrast to the periodic inappropriate laughing, apathy and anhedonia were markedly present. During the examination, the patient could not recall anything she would do or even think of with pleasure. According to the heteroanamnesis, she lost her interest in activities she used to like, did not go out with friends anymore, and showed no signs of joy or intimacy towards her family members either.

Along with the affective hyporesponsiveness, amotivation and a general psychomotor slowing were observed. Hypobulia, void perspectives, and lack of motivation were explored. Parental statements indicated that the patient’s social activity had continued to diminish, and her appearance and personal physical hygiene had deteriorated. When we initiated a conversation, the patient was negativistic and agitated. Her critical thinking ability was reduced, which led to inappropriate behavior (she, e.g., unexpectedly stood up and left the room while the examination was still ongoing). Considering her status, she was admitted to the clinic after her first visit.

After several differential diagnostic tests were performed (e.g., routine diagnostic laboratory parameters, immune serological analyses, electroencephalogram, magnetic resonance imaging, genetic testing), all the possible common and rare disorders, such as Huntington’s disease, Niemann Pick C disease, mitochondrial disorders, and autoimmune diseases, were ruled out.

At first contact, to differentiate the symptoms and severity of putative schizophrenia, we mapped the positive, negative, and general symptoms, as well as a clinical impression, using the Positive and Negative Syndrome Scale (PANSS), the Scale for Assessment of Negative Symptoms, and the Clinical Global Impressions-Severity (CGI-S) ( Groth-Marnat, 2009 ).

The patient had a very high PANSS total score, which corresponded to being considered “severely ill” or “among the most severely ill’ on the CGI-S ( Leucht et al., 2005 ). The PANSS score was derived dominantly from the negative items of the scale. Overall, her negative symptoms fulfilled criteria for predominantly negative symptoms, meaning that positive symptomatology was reduced, while negative symptoms were more explicit and dominated the clinical picture ( Riedel et al., 2005 ; Olie et al., 2006 ; Mucci et al., 2017 ). Baseline rating scale sores are presented in Table 1 .

Table 1 Summary of symptom scale scores at the time of admission to the hospital.

The diagnosis of EOS with predominantly negative symptoms was given and treatment with the antipsychotic agent cariprazine was initiated. The patient was hospitalized for 2 weeks following her arrival at the clinic. Cariprazine was started at the dose of 1.5 mg/day and titrated up to 4.5 mg/day over a 2-week period: the patient received 1.5 mg/day for the first 3 days, 3 mg/day from day 4 to day 12, and eventually 4.5 mg/day from day 13 onward. During these 2 weeks, which were spent in hospital, the patient’s explicit negative symptoms such as poverty of speech, psychomotor retardation, poor eye contact, and affective nonresponsiveness improved; however, delusions and hallucinatory perceptions did not fade significantly.

Two weeks after discharge, we saw the patient for her first outpatient visit. Significant clinical improvement was observed. The patient calmly cooperated during the examination, with no signs of agitation. She was oriented to time, place, and self, attention could be drawn and directed, and she was able to keep a target idea and change the subject. Although according to the family, perceptual disturbances were still present, laughing with no reason and looking aside were much less frequent, and restlessness of the legs had stopped; these symptoms were not observed during the examination. Psychomotoric negativism had improved greatly, the patient was more communicative, and she paid more attention to the activities of family members. The pace of speech was close to normal: the thinking latencies and slowed movement responses as observed at admission were not seen anymore. The patient had adequate reaction time to questions asked and could focus in the interview. Mild obstipation and somnolence in the evening were her main complaints. Apart from some tick-like eye closures, there was no pathological finding during physical and neurological examination. At this point, cariprazine was reduced to 3 mg per day.

At her second outpatient visit, which occurred 8 weeks after treatment initiation, further improvement was observed. According to her mother, the patient was more active and open at home. Neurological examination found that the alternating movements of her fingers were slightly slowed. Cariprazine 3 mg/day was continued with concomitant anticholinergic medication.

At the third outpatient visit, which occurred 16 weeks after the first contact, the patient’s overall symptoms, including cognitive functions, such as memory and abstract thinking, as well as functions in activities of daily living, had improved remarkably. She had started to participate in the family’s daily life, even taking responsibility for some household duties; further, she went to the hairdresser for the first time in years, a step forward from her previous state of self-neglect. She was probably still having auditory hallucinations, which she considered natural, and some extrapyramidal symptom (EPS)-like ruminating movements, like to-and-fro swinging of her trunk, were observed. She did not look aside any more and tics were no longer present. Compared with previous visits overall, she was very relaxed, retained eye contact, cooperated, and communicated adequately during the interview. She started to develop insight into her condition, and she told us that her “thoughts were not healthy.” At the last two visits, the synkinesis of the arms was reduced.

After 16 weeks of treatment, the patient’s PANSS Negative Subscale Score and PANSS factor score for negative symptoms (PANSS-FSNS) score were reduced by 44.44% and 41.31%, respectively. Recent studies have demonstrated that linking the percentage improvement of PANSS with CGI-S and -Improvement (CGI-I) scores shows that a 25–50% reduction of PANSS scores corresponds to clinically meaningful change ( Correll et al., 2011 ; Fusar-Poli et al., 2015 ). In acutely ill patients with predominantly positive symptoms who are more likely to respond well to treatment, the 50% cutoff would be a more clinically meaningful criterion; however, since even slight improvement might represent a clinically significant effect in a patient with atypical schizophrenia, the use of 25% cutoff is justified ( Correll et al., 2011 ; Fusar-Poli et al., 2015 ).

In this regard, the 44.44% (change from baseline: −20) and 41.31% (change from baseline: −19) improvement demonstrated on PANSS Negative Symptom subscale and PANSS-FSNS, respectively, are considered a clearly clinically relevant change. Beyond the impaired synkinesis and alternating movement of the arms and fingers, there were no other treatment-related physical dysfunctions. Change from baseline on the PANSS and CGI scales are shown over the course of treatment in Table 2 .

Table 2 Summary of symptom scale scores at weeks 16, 32, and 52.

Since our patient’s symptoms demonstrated strong improvement and tolerability was favorable, cariprazine therapy was continued. Improvement in both negative and positive symptoms was maintained over the course of treatment. At her later visits (32 and 52 weeks), PANSS total score was reduced to a level that was close to the minimum, and the decrease in negative symptom scores was considerable (PANSS-NSS=66.67% and PANS-FSNS=70.00% at both time points). The patient’s progress was also reflected in clinical and functional measurements, with the CGI-S score reduced to 2 (borderline mentally ill) and a CGI-I score of 1 (very much improved) indicating notable improvement.

Cariprazine has demonstrated broad spectrum efficacy in the treatment of positive and negative symptoms of schizophrenia. In a field where no treatment is available for difficult-to-treat negative symptoms, this case is unique and may have important implications for schizophrenia treatment. Despite experiencing approximately 8 years of untreated symptoms and functional impairment associated with predominantly negative symptom EOS, our 23-year-old female patient showed considerable symptomatic and functional improvement after several weeks of treatment with cariprazine. Given that the duration of untreated negative symptoms is associated with worse functional outcomes ( Boonstra et al., 2012 ), the remarkable improvement seen in this case shows how valuable cariprazine could be for patients with similar symptom presentations. Although it is not possible to generalize the observations and findings of this single case, it has the novelty of detecting a potential effect of cariprazine in a drug-naïve patient with marked negative symptoms of early-onset schizophrenia. To our knowledge, no cariprazine-related data has been published in this type of patients. A single case study is obviously far from being predictive for the efficacy of a drug, however, the results seen with this case are promising. With a dose recommended for patients with negative symptoms, our patient’s clinical condition, including positive, negative, and cognitive symptoms, as well as social functioning have improved notably, with the effect maintained for over 12 months. Generally, cariprazine has been well tolerated, with mild EPS observed after 8 weeks, but no metabolic, cardiac, or other side effects.

This case report suggests that the management of patients with EOS and prominent negative symptoms is achievable in everyday practice with cariprazine. More real-world clinical experience is needed to support this finding.

Data Availability Statement

All datasets generated for this study are included in the article/supplementary material.

Ethics Statement

Written informed consent was obtained from the individual(s), and minor(s)’ legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.

Author Contributions

All authors listed have made substantial, direct, and intellectual contribution to the work and approved it for publication.

This work was supported from Research and Technology Innovation Fund by the Hungarian National Brain Research Program (KTIA_NAP_ 2017-1.2.1-NKP-2017-00002). Editorial support for this case report was supported by funding from Gedeon Richter. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest.

Acknowledgments

We are thankful to the patient and her family for giving us the opportunity to share her story in the form of a publication. Also, we acknowledge editorial assistance was provided by Carol Brown, MS, ELS, of Prescott Medical Communications Group, Chicago, Illinois, USA, a contractor of Gedeon Richter plc.

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Keywords: cariprazine, schizophrenia, negative symptoms, early-onset schizophrenia, second-generation antipsychotic

Citation: Molnar MJ, Jimoh IJ, Zeke H, Palásti Á and Fedor M (2020) Early-Onset Schizophrenia With Predominantly Negative Symptoms: A Case Study of a Drug-Naive Female Patient Treated With Cariprazine. Front. Pharmacol. 11:477. doi: 10.3389/fphar.2020.00477

Received: 24 October 2019; Accepted: 26 March 2020; Published: 23 April 2020.

Reviewed by:

Copyright © 2020 Molnar, Jimoh, Zeke, Palásti and Fedor. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Maria Judit Molnar, [email protected]

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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Case study: A patient with severe delusions who self-mutilates

Lesiba t. lebelo.

2 Department of Psychiatry, School of Medicine, University of Pretoria, Pretoria, South Africa

Gerhard P. Grobler

1 Department of Psychiatry, Mamelodi Hospital, Pretoria, South Africa

Associated Data

Data sharing is not applicable to this article as no new data were created or analysed in this study.this study.

Background and introduction

Although some overlapping features exist between self-injury and intention to die, there is growing recognition that non-suicidal self-injury (NSSI), including major self-mutilation (MSM), and suicidal behaviour are distinct entities as evidenced by their significance in terms of aetiology, psychiatric impairment, psychological function, method of self-harm and course or outcome between the two phenomena. 1

We present a case of self-harm in a mental healthcare user diagnosed with schizophrenia to highlight the distinction made above.

Case presentation

Mr X is a 38-year-old, unemployed, single male with no children and with an elementary level of education. This was his index presentation with a 4-year history characterised by ongoing persecutory delusions, as well as auditory hallucinations. He was brought to the Emergency Department by ambulance because he was found to be bleeding profusely from his scrotum in the toilet of a petrol filling station. He alleged that he had cut open his scrotum to remove his testicles before his ‘tormentors’ could do so. He stated clearly that he did not want to die because he valued his life. This was therefore not an attempt at suicide.

He was initially admitted to the urology ward and then referred to psychiatry. The multi-disciplinary team diagnosed him with and treated him for schizophrenia. He responded well to haloperidol 2.5 mg orally in the morning and 5 mg orally at night. A long-acting injectable antipsychotic, flupenthixol decanoate 20 mg intramuscular was also prescribed. No adverse effects were reported. Lorazepam was titrated downwards from 1 mg orally twice daily to 1 mg orally at night, and then stopped before he was discharged. Lansoprazole 30 mg daily orally, tramadol 50 mg three times daily orally and paracetamol 1 g orally were also prescribed as needed.

Upon discharge, on day 44 of the admission, the patient was symptom free with no psychotic or anxiety features.

The patient did not manifest any depressive symptoms throughout his hospitalisation, nor on his 4-week follow-up visit subsequent to discharge. He also demonstrated full and complete understanding that the voices, the self-conviction and his belief that people were coming to harm him were all part of his illness called schizophrenia. He also demonstrated full understanding that the belief of being harmed and people conspiring against him were also part of his schizophrenic illness that had been untreated for at least the past 4 years. With no negative emotion, he demonstrated intellectual understanding with unconditional acceptance of his illness. We emphasised to him that he must be consistent with medical check-ups at his local clinic as some other medical conditions can cause his illness to resurface. It was further emphasised to him that for as long as he took his treatment regularly and as prescribed the schizophrenia would be managed and controlled well. He agreed to stay away from all psychoactive substances. This user was amenable to following up with a clinical psychologist, an occupational therapist and a social worker.

He was followed up 1 month later and then referred to his local clinic for continuation of the prescribed treatment, appointments for continuation of psycho-education, counselling and relevant psycho-therapies. This patient responded well and remitted only on antipsychotic agents.

Literature review and discussion

In a study of measurable variables, paranoia and auditory hallucinations, psychotic-like experience (PLE) and stressful life events all contributed to the patient causing self-harm. Compared to those without PLEs, the prevalence of NSSI was higher than those with PLEs. 1

Psychotic-like experiences are highly prevalent in the general population, with figures of 20% or above being reported in some studies. 1 Major self-mutilation (or NSSI) is a rare but potentially catastrophic complication of severe mental illness. Most people who inflict NSSI have a psychotic disorder, usually a schizophrenia spectrum psychosis. It is not known when in the course of psychotic illness, NSSI is most likely to occur. 2 In general, schizophrenia is associated with worse social functional outcomes compared with other psychotic disorders, but the few studies that directly tested this assumption by comparing the longitudinal courses of social functioning in affective and non-affective psychoses have yielded conflicting findings. 3

Cases of genital self-mutilation reported in the literature have been in patients with psychosis, including schizophrenia. 4 Our own literature review found only a few case reports, published in 1974 (a female patient with schizophrenia and erotomania), 1986 (autocastration with biblical delusions) and in 1995. Greilsheimer writes that: ‘Men who intentionally mutilate or remove their own genitals are likely to be psychotic…’. 5

The reason for presenting the case is that there was no similar case recorded in our country, using Google Scholar search engine database of at least the past 5 years, nor elsewhere when we searched using the following keywords: ‘Self-castration, non-suicidal self-injury and psychosis, self-castration due to psychosis’.

In the South African context, the promulgation of the Traditional Health Practitioners Act no. 35 of 2004 has become an important precipitant for the local review of the place of culture and religion/spirituality in secular areas such as health, mental health and spirituality. 6 Our patient did not display delusions with religious or spiritual content. This particular patient was not practising any religion although he claims to believe in God. He emphasised that he was convinced by his delusions and hallucinations that some people known to him were conspiring to cut his scrotum and extract his testicles for some ritualistic practices. Their psychosis can eventually weaken their faith as they may think that they have been successfully bewitched and cursed even if they have been mentally stabilised.

Patients living with schizophrenia and who suffer persistently high levels of psychotic symptoms as well as poorer (psychosocial) functioning and lower self-esteem have higher severity of suicide behaviour. 7 Even in first episode psychosis, one in 10 people engages in self-harm. 8

It is important to take note of this case as it is the first of its kind and adds to existing knowledge in mental health that untreated and long-standing psychosis can result in the patient harming himself irreversibly such that they lose the capacity to reproduce.

Despite the vulnerable position of the testicles, testicular trauma is relatively uncommon. The mobility of the scrotum may be one reason, severe injury is rare. Given the importance of preserving fertility, traumatic injuries of the testicles deserve careful attention. Testicular injuries can be divided into three broad categories based on the mechanism of injury: (1) blunt trauma, (2) penetrating trauma and (3) degloving trauma. Such injuries are typically seen in males aged 15–40 years.

Our patient was psychotic with auditory hallucinations, persecutory delusions and bizarre delusions which did not include religious delusions when he harmed himself. He was convinced that his ‘tormentors’ were listening to his thoughts and he consequently planned to cut open his scrotum to remove his testicles before they could do that to him. The main reason our patient injured himself was not to die but to relieve himself of the constant and increasing threats of being robbed of his testicles. It is important in the South African context to treat a psychiatric patient by using the multi-disciplinary team approach which is also holistic in nature and covers all aspects of mental healthcare service provision, including spirituality, as most citizens (92%) of South Africa expressed religious affiliation. 9

Not all patients who harm themselves, even severely, are suicidal. Some just want to rid themselves of tormenting psychosis as in this case.

Acknowledgements

The authors wishes to acknowledge their colleagues who supported this project and their patients from whom they learnt much.

Competing interests

The authors have declared that no competing interest exists.

Authors’ contributions

Both authors contributed equally to this work.

Ethical consideration

This article followed all ethical standards for research without direct contact with human or animal subjects.

Funding information

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data availability statement

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of any affiliated agency of the authors.

How to cite this article: Lebelo LT, Grobler GP. Case study: A patient with severe delusions who self-mutilates. S Afr J Psychiat. 2020;26(0), a1403. https://doi.org/10.4102/sajpsychiatry.v26i0.1403

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Schizophrenia(Case study research); a review with patient diagnosis outcome and treatment. Time to change

2020, ncbi.nlm.nih.gov

This is a case of Charlie a 25-year-old male, single, Fillipino, Roman Catholic, from Paquibato Dist, Davao City. He was home schooled, currently not employed, previously diagnosed on September 2nd 2019 as schizophrenia in IPBM hospital.

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Article Contents

Introduction, external influences, 1997–2003, conclusions, conflict of interest.

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National Institute of Mental Health Support for Cognitive Treatment Development in Schizophrenia: A Narrative Review

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Robert K Heinssen, Sarah E Morris, Joel T Sherrill, National Institute of Mental Health Support for Cognitive Treatment Development in Schizophrenia: A Narrative Review, Schizophrenia Bulletin , Volume 50, Issue 5, September 2024, Pages 972–983, https://doi.org/10.1093/schbul/sbae109

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For several decades the National Institute of Mental Health (NIMH) has supported basic and translational research into cognitive impairment in schizophrenia. This article describes the Institute’s ongoing commitment to cognitive assessment and intervention research, as reflected by three signature initiatives—Measurement and Treatment Research to Improve Cognition in Schizophrenia; Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia; and Research Domain Criteria—and related funding announcements that span basic experimental studies, efficacy and comparative effectiveness trials, and implementation research designed to promote cognitive healthcare in real-world treatment settings. We discuss how trends in science and public health policy since the early 2000s have influenced NIMH treatment development activities, resulting in greater attention to (1) inclusive teams that reflect end-user perspectives on the utility of proposed studies; (2) measurement of discrete neurocognitive processes to inform targeted interventions; (3) clinical trials that produce useful information about putative illness mechanisms, promising treatment targets, and downstream clinical effects; and (4) “productive urgency” in pursuing feasible and effective cognitive interventions for psychosis. Programs employing these principles have catalyzed cognitive measurement, drug development, and behavioral intervention approaches that aim to improve neurocognition and community functioning among persons with schizophrenia. NIMH will maintain support for innovative and impactful investigator-initiated research that advances patient-centered, clinically effective, and continuously improving cognitive health care for persons with psychotic disorders.

In 1992, the Schizophrenia Bulletin published several prescient articles and commentaries on the theme of cognitive therapy for schizophrenia. 1–7 These papers signaled fresh interest in interventions for improving attention, memory, learning, and problem-solving among persons with schizophrenia, and considered a variety of biobehavioral approaches to promote greater clinical, social, and vocational recovery. The authors’ perspectives on key questions about cognitive interventions (eg, cognitive targets, mechanisms of treatment effects, and implementation barriers); clinical research methods (eg, ecologically valid measures, trial designs, and mediation analyses); and alliances to promote uptake of effective practices (eg, partnerships between service users, family members, clinicians, and scientists) foreshadowed later efforts by the National Institute of Mental Health (NIMH) to promote cognitive treatment development in psychosis.

The present article summarizes NIMH initiatives since the early 2000s that aimed to facilitate cognitive intervention research for schizophrenia and related disorders. We first describe external developments between 1997 and 2003 that motivated NIMH to explore new tactics for stimulating treatment development research. We then examine specific NIMH initiatives between 2002 and 2012 that catalyzed cognitive measurement, drug development, and rehabilitation research aimed at improving neurocognition and community functioning in schizophrenia. Next, we consider recent science and policy developments intended to speed treatment development research along the discovery-translation-implementation pathway. We conclude by summarizing lessons that may benefit future efforts to advance patient-centered, clinically effective, and continuously improving cognitive health care for persons with psychotic disorders.

NIMH is the lead government agency in the United States for research on mental disorders. In setting its scientific priorities, the Institute considers input from diverse external sources, including other federal agencies, the extramural research community, advocacy and professional organizations, clinical providers and health system administrators, and persons who use mental health services. The period between 1997 and 2003 was a fertile time for interaction, with synergistic initiatives by the US Surgeon General, a Presidential Commission, and the Director of the National Institutes of Health (NIH) that convened diverse constituents to consider mental health and clinical research ecosystems and to recommend strategies for improving links between science and services.

The Surgeon General’s Report on Mental Health, 8 initiated in 1997, was an ambitious effort to summarize scientific evidence underlying the epidemiology, diagnosis, and treatment of mental disorders, and to describe gaps between what is known through research and application of advances in real-world settings. Based on an extensive review of the literature, the report conveyed optimism about the research supporting the efficacy and range of treatments available for many disorders. While the Surgeon General recommended strongly that people seek help for mental disorders, 9 the report highlighted important areas of scientific uncertainty. The Surgeon General called for continued investment in mental health research, emphasizing integrative neuroscience and molecular genetics studies to identify novel targets for pharmacologic and psychosocial interventions as well as new approaches to health services implementation research.

The President’s New Freedom Commission on Mental Health (2002–2003) extended the Surgeon General’s analysis to include a comprehensive study of the US mental health service delivery system across public and private sectors. 10 The Commission recognized enormous progress in the scientific study of interventions for mental disorders but noted an absence of cures and spotty implementation of evidence-based services in real-world settings. The Commission’s final report advocated a major, long-term commitment to basic research to promote recovery and resilience, and ultimately to cure and prevent mental illness. It also emphasized the need for applied research to study the dissemination, implementation, effectiveness, and sustainment of evidence-based interventions in communities, and to speed testing of emerging innovations in field settings. 11

The NIH Roadmap initiative, launched by the NIH Director in 2002–2003, reexamined the NIH research portfolio to identify scientific gaps and to consider novel methods, technologies, and large-scale projects to transform the process of medical research. 12 The Roadmap engaged hundreds of NIH staff, extramural scientists, and the lay public in a deliberative process of assessing scientific challenges, enumerating roadblocks to progress, and proposing bold ideas to increase the efficiency and impact of biomedical research. Three major themes—ie, new pathways to discovery, research teams of the future, and reengineering the clinical research enterprise—organized initiatives to promote state-of-the-art technologies, interdisciplinary team science, and clinical research via academic-community partnerships. Collectively, these programs aimed to speed the movement of research from the laboratory to the patient’s bedside within a decade. 13

Impact of External Initiatives on NIMH Treatment Development Activities

NIMH leaders and scientist administrators engaged actively in committees, work groups, and public meetings that supported the Surgeon General’s Report, the President’s New Freedom Commission, and the NIH Roadmap process. NIMH staff contributed to planning, convening, synthesizing, and reporting activities, learned new approaches from government and private sector partners, and adopted several best practices in subsequent cognitive treatment development efforts:

Include Key Partners.

All 3 external projects recognized the need for broad input and new partnerships to understand and address complex medical problems. 8 , 10 , 12 In addition to representatives from academia and government, nontraditional experts were included, such as persons with lived experience, professionals with practical experience in organizing, delivering, and financing mental health services, and representatives of private foundations and patient advocacy organizations. The Surgeon General’s report 8 and the NIH Roadmap 12 advocated stronger partnerships with biotechnology and pharmaceutical industries and greater collaboration between federal agencies with shared responsibilities for developing, regulating, and delivering evidence-based treatments.

Promote Transparency.

The New Freedom Commission utilized several tactics to increase transparency, including open meetings, regular opportunities for public input, and timely reports from subcommittees and the overall Commission. 11 For example, monthly working meetings included open deliberation and dedicated time for public testimony from advocacy groups, professional organizations, and members of the public. In addition, an interactive public website encouraged participation outside in-person meetings; over 2300 individuals submitted comments, concerns, and ideas for consideration. Finally, detailed reports from 15 subcommittees were made available, along with an interim progress report 14 that generated spirited commentary that influenced the final phase of the Commission’s work.

Encourage “Productive Urgency”.

The cadence, operations, and deliverables of the President’s New Freedom Commission and the NIH Roadmap set new standards for rapid policy analysis and strategic planning. Aggressive one-year timelines were established to direct effort to urgent problems in mental health delivery systems 11 as well as respond to heightened public expectations for NIH-supported research. 12 Subcommittees and working groups, comprised of government and private sector experts with relevant expertise, tackled key issues in parallel, with overall coordination of efforts by Commissioners and NIH leaders, respectively. This formula was successful in generating understandable goals, concrete recommendations, and performance benchmarks for assessing the impact of new initiatives. 13 , 15 The urgency, efficiency, and productivity that characterized these initiatives influenced NIMH’s ensuing efforts to spur cognitive treatment development research in schizophrenia.

NIMH Cognitive Treatment Development Initiatives, 2002–2012

The Surgeon General’s report identified cognitive dysfunction as a key feature of schizophrenia and noted a paucity of evidence-based treatments for cognitive symptoms. 8 Hyman and Fenton 16 echoed these observations and suggested cognitive impairment as a “test case” for new approaches to schizophrenia therapeutics. Specifically, they proposed a framework for drug and psychosocial intervention development that would (1) dissect schizophrenia into component symptom complexes such as cognitive deficits; (2) develop measures to define new clinical targets as endpoints in human clinical trials; (3) direct interventions at the narrower clinical targets; (4) employ novel experimental designs to evaluate efficacy and clinical significance; and (5) draw on cognitive neuroscience and neuroimaging research to clarify neural mechanisms involved in cognition and to develop objective biomarkers for cognitive deficits. Hyman’s and Fenton’s commentary signaled a new approach to assessment and treatment development in schizophrenia that influenced NIMH initiatives over a 10-year period.

Measurement and Treatment Research to Improve Cognition in Schizophrenia

In 2002, NIMH announced the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative, a multiyear effort to identify and remedy barriers to drug development and testing for cognition in schizophrenia. 17 Following a competitive selection process, a contract was awarded to UCLA (Stephen Marder and Michael Green, co-principal investigators) to engage the pharmaceutical industry, the academic community, and government agencies, including the US Food and Drug Administration (FDA), in a consensus-oriented process to identify cognitive targets for intervention; select reliable and valid neuropsychological measures to assess cognition as a dependent variable in treatment trials; propose experimental designs to establish the efficacy of agents to enhance cognition in schizophrenia; and identify potential molecular targets for new therapeutic agents. The contract mechanism allowed a high level of collaboration between NIMH staff and the MATRICS team to pursue these goals. Importantly, coordinated efforts between NIMH leaders and MATRICS investigators spurred conversations and new alliances among key actors in the drug development space, including psychopharmacologists, 18 the FDA, 19 and persons with lived experience. 20

The MATRICS team convened 6 interlocking conferences over a 2-year period, with timely reports that conveyed the focus, process, and outcomes of each meeting. 18 , 19 , 21–23 Concrete achievements that sprang from these activities include the following:

The MATRICS Consensus Cognitive Battery (MCCB) was developed using quantitative analyses and expert consensus methods and was field tested in a 5-site psychometric and validation study. 24 To facilitate interpretation of results using a common scaling across tests, the MCCB was co-normed using data obtained from a representative US community sample. 25

To meet the FDA’s requirement for functionally meaningful co-primary measures in cognitive intervention trials, 4 potential measures were evaluated alongside the MCCB for reliability, utility, practicality, and relationship to cognitive performance. 26

In 2005, the NIMH National Advisory Mental Health Council (NAMHC) and the FDA recommended the MCCB as the standard cognitive performance battery in clinical trials of potential cognition-enhancing interventions. 24

The MCCB has been translated into over 39 languages 27 and is now widely used to assess neurocognition in schizophrenia clinical studies. Since 2004, the MCCB has been cited in ~500 scientific publications and included as an outcome measure in ~170 clinical studies registered in ClinicalTrials.gov.

The FDA-NIMH-MATRICS workshop on clinical trial design for neurocognitive drugs for schizophrenia 19 developed guidelines for subject selection, co-primary outcome measures, and statistical approaches for clinical trials involving cognitive-enhancing drugs, which were later updated based on practical experience. 28

The MATRICS initiative was successful in catalyzing studies of procognitive drugs in schizophrenia, but new medications have proved elusive. 29 Green et al 30 , 31 reviewed cognitive intervention studies launched since MATRICS and identified several methodological factors that may hinder efforts to identify efficacious drugs. Those authors also noted broader scientific issues that impede drug discovery, including our incomplete understanding of the pathophysiology of cognitive impairment and error variance attributed to clinical and functional heterogeneity across schizophrenia spectrum disorders. 31 Two ensuing NIMH initiatives considered these important scientific considerations in turn.

Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia

The final meeting of the MATRICS program focused on new preclinical and clinical research approaches for assessing and improving cognition in schizophrenia. 23 A strong case was made for applying methods derived from experimental cognitive psychology and cognitive neuroscience to examine the integrity of specific cognitive systems implicated in schizophrenia and to directly measure the effects of drugs on cognition-related brain activity. 32 Responding to these recommendations, Cameron Carter and Deanna Barch proposed the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) conference series 33 and were awarded consecutive research conference grants to articulate a neuroscience research agenda that would extend the work started by MATRICS.

Between 2007 and 2011 the CNTRICS steering committee organized 7 meetings that brought together experts from the basic and clinical sciences, researchers from academia and industry who use animal models, and individuals with experience in clinical trials, psychometrics, and cognitive rehabilitation in schizophrenia to explore potential benefits of using constructs, tasks, and tools from cognitive neuroscience to better understand and treat cognitive impairments in psychosis. 34 , 35 Interactive surveys, quantitative summaries, and consensus-building methods were employed across meetings to identify cognitive systems and component processes that could serve as targets for measurement and treatment development; to address psychometric issues relevant for adapting experimental cognitive tasks for use in clinical trials; to select candidate experimental tasks that measure key cognitive constructs implicated in schizophrenia; to consider promising imaging biomarkers for use in cognitive treatment development research; and to facilitate development of translational animal model paradigms for exploring cognitive and affective constructs. In addition, the steering committee introduced an innovative buddy system that paired prominent cognitive neuroscientists with well-known clinical researchers with schizophrenia expertise to maintain a patient-centered focus in CNTRICS deliberations.

Midway through the CNTRICS process, NIMH published a funding opportunity announcement to solicit proposals for research aimed at adapting and optimizing experimental cognitive measures for use in treatment trials of schizophrenia (RFA-MH-08-090). Among the studies selected for funding, a 5-site collaborative project came together as the “Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia (CNTRaCS) Consortium.” CNTRaCS investigators proposed a transdisciplinary approach for (1) cognitive task selection; (2) adaptation of validated paradigms for clinical research; (3) psychometric evaluation of new measures; and (4) maintaining construct validity of modified tasks. Since 2008, CNTRaCS has pursued translational measurement development for cognitive constructs identified in CNTRICS (ie, goal maintenance; relational encoding and retrieval in episodic memory; gain control; visual integration; working memory; and reinforcement learning) and produced a variety of cognitive neuroscience-based approaches for clinical research studies, including imaging biomarkers. 36

Together, CNTRICS and CNTRaCS achieved the respective goals of establishing a neuroscience research agenda for cognitive treatment development in schizophrenia and adapting validated laboratory tasks of cognitive operations for use in clinical trials. Over 60 scientific publications describe the scientific discourse that occurred during CNTRICS meetings as well as methods, results, and products from the CNTRaCS research program. Cognitive task paradigms developed by CNTRaCS are freely available to the field and industry ( https://cntracs.ucdavis.edu/ ), including tasks and associated computational models appropriate for clinical trials as well as research conducted within the NIMH Research Domain Criteria framework. 37

Research Domain Criteria

NIMH launched the Research Domain Criteria (RDoC) initiative in 2009 to provide a framework for research that explores novel ways of characterizing and classifying mental disorders. The rationale for this new approach was that the ecosystem of research funding, peer review of grant applications and scientific publications, and regulatory activities was over-focused on studies of highly heterogenous mental disorders as defined in longstanding diagnostic systems. The overarching RDoC hypothesis is that mental disorders may be better understood if the tools and concepts of modern behavioral neuroscience are used to dissect heterogeneity within psychopathology and assess functional domains that could be targeted for treatment in a more precise and individualized way.

The RDoC framework was informed by a series of workshops in 2010–2012—and an additional workshop in 2018—which closely modeled the MATRICS and CNTRICS meetings. These workshops engaged over 200 leading scientists and NIMH staff in discussions of the RDoC approach and the development of a set of exemplar constructs and associated elements that provide a shared vocabulary for this scientific endeavor. The first workshops focused on Working Memory 38 and Cognitive Systems, 39 built directly on the knowledge base created by CNTRICS. These workshops adopted CNTRICS’ focus on integrating knowledge from cognitive and affective neuroscience into novel approaches for translational research, a focus that persisted throughout the workshop series. In contrast to MATRICS, NIMH did not develop a formal battery of specified tasks for assessing RDoC domains but instead encouraged investigators to flexibly select measures that are fit for purpose. Participants in this series of formative RDoC workshops populated the RDoC matrix with exemplars of tasks and tools, including several CNTRaCS tasks, which could be used to assess constructs related to RDoC cognitive systems domains.

NIMH has published 19 RDoC-focused funding opportunity announcements since 2011. More than one hundred research projects adopting RDoC principles have been funded, along with many others awarded under other NIH funding mechanisms. Among these grants are several projects that examine cognitive constructs such as language 40 and perception 41 in psychosis which may lead to novel treatment targets or outcome measures. Most recently, the NIMH RDoC Unit launched the Individually Measured Phenotypes to Advance Computational Translation in Mental Health (IMPACT-MH) initiative (RFA-MH-23-105). Projects supported through IMPACT-MH will combine data from cognitive tasks and device-based behavioral measures with electronic health records information to derive novel clinical signatures that can be assessed at the individual level to improve clinical decision-making and predict clinical outcomes.

NIMH Workshop on Cognitive Training in Mental Disorders

During the period when MATRICS/CNTRICS/RDoC initiatives were being developed (2002–2012), NIMH observed growing interest among extramural scientists for nonpharmacologic cognitive training and rehabilitation interventions, with successful research proposals involving patients from diverse diagnostic categories and across developmental stages. In addition, an annual conference sponsored by the Columbia University Irving Medical Center brought together researchers, clinicians, and healthcare administrators to share experiences and perspectives on cognitive remediation in psychiatry and to focus attention on emerging translational, clinical, and implementation research questions. 42 To learn from the expanding cadre of cognitive interventionists, NIMH convened a state-of-the-science meeting in 2012 to review evidence for the efficacy of cognitive training approaches across psychiatric illnesses, including schizophrenia, and to identify knowledge gaps, new research opportunities, and examples of research-to-practice implementation. 43 The workshop included investigators from academia, military research agencies, and the NIMH Intramural Research Program; representatives of digital health companies, state mental health authorities, and community behavioral health systems; and health scientist administrators from several NIH institutes. Approximately one-quarter of participants were veterans of the MATRICS, CNTRICS, and/or RDoC initiatives, which provided valuable scientific continuity.

For purposes of the workshop, cognitive training (CT) was differentiated from other behavioral and psychosocial interventions that address problematic cognitions as part of a broader therapeutic approach, such as cognitive behavioral therapy or psychoeducation. CT was defined more precisely as “an intervention that uses specifically designed and behaviorally constrained cognitive or socio-affective learning events, delivered in a scalable and reproducible manner, to potentially improve neural system operations.” 44 The workshop addressed the current state of knowledge regarding (1) the neuroscience basis for cognitive, affective, and neural processes targeted by CT; (2) evidence of CT efficacy for improving neurocognitive processes and functioning; (3) hypothesized mechanisms of CT treatment effects; (4) approaches that combine CT with other treatment modalities; (5) predictors of treatment response; and (6) what has been learned from efforts to implement CT in clinical practice.

Keshavan et al. summarized the workshop’s presentations, discussions, and recommendations for future research. 44 The authors concluded that “overall, the evidence thus far supports the neurobiological rationale and the efficacy of cognitive training in schizophrenia, but replication of positive results is needed; many questions remain with regard to therapeutic mechanisms, key therapeutic ingredients, and approaches to dissemination in routine clinical settings.” Several considerations for the design of CT trials echo lessons from the MATRICS initiative 29 , 31 ; ie, the importance of detailed participant characterization, including baseline cognitive functioning; choosing appropriate inclusion/exclusion criteria; measuring specific (vs global) cognitive operations as treatment targets and outcomes; and accounting for mediators, moderators, and mechanisms of treatment effects. Other recommendations emphasized up-front attention to end-user perspectives, clinical workflows, and provider requirements in intended delivery settings, and including outcome measures that are meaningful to healthcare policymakers. Together, these recommendations encouraged best practices for advancing interventions that target core neurocognitive operations necessary for clinical, social, and educational/vocational recovery, and for positioning new interventions for rapid adoption in clinical practice.

Impact of NIMH Cognitive Treatment Development Initiatives

The MATRICS, CNTRICS, and RDoC initiatives were largely successful in replicating the inclusiveness, transparency, and productive urgency that characterized the Surgeon General’s Report, the President’s New Freedom Commission, and the NIH Roadmap. Each NIMH initiative brought together diverse constituents to work through complex scientific questions, and through progressive encounters, to establish a common framework and vocabulary for analyzing problems and imagining potential solutions. Frederick Frese, a respected mental health “prosumer,” contributed significantly to the MATRICS Neurocognition Committee 24 as a champion of recovery principles 20 and stigma-free, nonpejorative language about cognition in schizophrenia. 45 The unique value of this lived experience perspective prompted NIMH to encourage similar engagement with service users in subsequent research initiatives, as described below.

The cadence of MATRICS, CNTRICS, and RDoC meetings, the continuity of participants across initiatives, and new collaborations among diverse partners fostered interdisciplinary teams that later tackled translational research goals. The co-creation of new research concepts, methods, and products by such teams were essential factors in generating broad enthusiasm for cognitive treatment activities in schizophrenia. Indeed, ~750 scientific papers, review articles, and book chapters have been published since 2002 that are based on MATRICS, CNTRICS, or RDoC contributions to the assessment and treatment of cognitive symptoms in schizophrenia.

Science and Policy Trends, 2013–2023

Between 2002 and 2012, NIMH-supported initiatives created momentum for neuroscience-based studies in schizophrenia that focused on illness mechanisms and targeted interventions based on mechanistic insights. A small number of competitive funding opportunities incentivized the development of new assessment tools and clinical trial methods, but most funded studies used traditional grant mechanisms to support investigator-initiated projects. In the subsequent decade, new science and NIMH policy developments influenced trends in cognitive intervention research, including new expectations for clinical trials and implementation of science studies.

Experimental Therapeutics Paradigm for Clinical Trials

By 2010, major pharmaceutical companies had exited the field of psychiatry, citing poor understanding of disease mechanisms, a lack of biomarkers and valid animal models, and high failure rates in clinical trials. 46 , 47 The dramatic change in industry priorities prompted NIMH to seek guidance on how to better align basic, clinical, and intervention research to support pharmacologic treatment development. The NAMHC workgroup report, “From Discovery to Cure” 48 recommended several changes to the NIMH clinical trials portfolio to accelerate translational efforts, including a shift towards an experimental therapeutics model, “in which interventions are used as probes of disease mechanisms as well as tests of efficacy.” 49

Since 2014, NIMH has solicited clinical trial applications through a dedicated set of funding announcements that cover the intervention development pipeline, including first-in-human and early-stage clinical trials of novel investigational drugs or devices; pilot research to develop and test innovative psychosocial interventions; confirmatory efficacy trials; and comparative effectiveness trials. In each case, an experimental therapeutics approach is required, where projects (1) identify a mechanistic target or mediator for the intervention being tested; (2) measure the intervention’s impact on the hypothesized target; and (3) examine whether changes in targets are associated with changes in distal clinical or services outcomes. Trials designed in this manner are informative for basic, translational, and intervention research in that studies produce useful information about putative illness mechanisms, promising treatment targets, and downstream clinical effects.

Implementation and Sustainment of Evidence-Based Interventions

Reports from the Surgeon General, 8 the President’s New Freedom Commission, 10 the Institute of Medicine, 50 and a NAMHC workgroup on mental health services research 51 all noted long delays between the reporting of scientific findings and the translation of new knowledge into clinical practice. To address this “implementation gap,” NIMH began promoting deployment-focused approaches to intervention development, testing, and dissemination, 52 starting with the Recovery After an Initial Schizophrenia Episode (RAISE) initiative. 53 Subsequent deployment-focused studies have considered the perspective of end-users (eg, service users, clinicians, health care administrators, and payers) and characteristics of the ultimate delivery settings (eg, workforce capacity, training resources, clinical workflows) to help ensure that proposed interventions are feasible and scalable, and that research results are actionable for improving practice.

This approach is elaborated in current NIMH research initiatives aimed at accelerating the implementation and continuous improvement of new practices in diverse, real-world healthcare settings, including the ALACRITY Research Centers 54 program, EPINET Research Networks, 55 and funding announcements for comparative effectiveness trials (eg, PAR-21-130; PAR-21-131). Through these initiatives, NIMH strongly encourages meaningful involvement of mental health service users and family members in multiple roles throughout the research enterprise. For example, serving as a principal or co-principal investigator of a research project; membership in a project’s executive committee or external advisory group; as a practice-partner member of a transdisciplinary research team; or as a research participant whose lived experience perspectives are systematically assessed via qualitative and/or quantitative methods.

Impact of Experimental Therapeutics and Implementation of Science Funding Announcements

Extramural scientists have successfully pivoted to experimental therapeutics trials to test cognitive interventions for persons with psychotic disorders, as evidenced by research grant projects awarded across all stages of the intervention pipeline. Many funded projects are taking cognitive treatment in new directions, including (1) interventions that target social cognitive processes; (2) approaches that combine cognitive training with other therapies to improve neurocognitive outcomes or promote generalization of training effects (eg, procognitive medications, neuromodulation techniques, aerobic exercise, or behavioral skills training); (3) studies that integrate cognitive interventions into treatment programs for early psychosis; and (4) efforts to address heterogeneity in neurocognitive functioning through personalized cognitive training.

Several deployment-focused implementation projects are examining the adoption and sustainment of cognitive training interventions in real-world community settings. For example, one ALACRITY Center subproject focuses on improving the accessibility and personalization of cognitive remediation for schizophrenia in publicly funded outpatient mental health clinics (P50MH115843). An EPINET network project is testing the feasibility and real-world effectiveness of a neuroscience-informed cognitive training program that pairs social cognitive training with a research-supported mobile application to improve outcomes in first-episode psychosis (R01MH120589). A third implementation project is testing an environmental intervention to bypass cognitive and motivational difficulties associated with schizophrenia to increase adherence to medications and improve functional outcomes among persons receiving treatment in community mental health centers (R01MH11701).

Reflections and Considerations for Future Research

Cognitive treatment development in the United States has progressed substantially since 1992, when thought leaders debated whether cognitive intervention in schizophrenia was possible and if so, how clinical studies should proceed. 1–7 In the ensuing decades, NIMH has employed both top-down and bottom-up approaches to support basic, translational, and implementation research in cognitive treatment for psychosis. The MATRICS, CNTRICS, and RDoC initiatives illustrate the former tactic, where NIMH staff collaborated closely with extramural scientists and others to organize a neuroscience research agenda around cognitive therapeutics. These efforts over a 10-year period helped to cultivate a vibrant learning community that embraced the challenges of delineating cognitive systems implicated in schizophrenia and developing new animal models, clinical assessments, and intervention methods. Afterwards, NIMH shifted its focus to standing funding announcements designed to support innovative and impactful investigator-initiated research projects. Over the past decade, the science supporting cognitive treatment efficacy and implementation has advanced and evolved, propelled by the interests, creativity, and energy of the extramural research community.

Partnerships with other government agencies, industry, and persons with lived experience have grown over time and continue to benefit NIMH treatment development activities. For example, the Accelerating Medicines Partnership Program for Schizophrenia (AMP SCZ) 56 is a public-private endeavor between NIMH, the FDA, the European Medicines Agency, pharmaceutical companies, and other private-sector partners to generate tools that will aid the development of early-stage treatments for people who are at risk for schizophrenia. Persons with lived experience contribute to the leadership and operation of AMP SCZ, which has enriched both the science and real-world relevance of the project. 57 , 58 This aspect of AMP SCZ is consistent with NIMH’s expanded vision of team science, which includes individuals with lived experience, family members, frontline clinicians, and payers as colleagues in clinical research efforts. 54 , 55 It is also an Institute priority to include members of historically underrepresented groups in team science, ie, persons from racial, ethnic, and sexual and gender minority groups as well as individuals from lower socioeconomic strata.

Collectively, external influences and NIMH initiatives have helped set a direction for the next phase of science-to-service research in cognitive treatment for persons with psychotic disorders. The 2023 White House Report on Mental Health Research Priorities, 59 developed to address the mental health crisis exacerbated by the COVID-19 pandemic, provides additional guidance. For example, the White House Report calls for new scientific efforts to (1) support and expand the supply, capacity, and diversity of the mental health workforce; (2) increase the availability, quality, and impact of evidence-based services across a range of settings; (3) foster long-term engagement in care and recovery among persons receiving mental health treatments; and (4) develop and test strategies for provider training, supervision, and performance feedback to ensure sustained implementation of high-quality interventions. To reduce mental health disparities and advance equity, the Report encourages research that addresses social determinants of health, applies community-based participatory methods to ensure the responsiveness of interventions, and oversamples members of historically underrepresented groups in mental health studies.

These priorities are highly relevant to cognitive treatment of psychosis in the United States, where the cognitive intervention workforce is small, evidence-based programs are rarely available outside of academic research clinics, and few individuals with lived experience receive needed therapies. A forward-looking collaboration between the New York State Office of Mental Health (OMH) and Columbia University 60 addresses these limitations through a multiyear project to implement cognitive health services in state-operated outpatient clinics for persons with serious mental illness (SMI). In a series of richly detailed papers, 61–66 Medalia, Saperstein, and colleagues describe a systematic process for introducing cognitive remediation practices in large systems of psychiatric care. Their deployment-focused, phased, and data-driven approach stands out as a case study in implementation excellence.

Table 1 presents current views about the stages of successful implementation, as summarized in the National Implementation Research Network’s synthesis of implementation research and practice studies, 67 as well as best practices for promoting the adoption, installation, and sustainment of evidence-based programs, 68 per guidance provided by the Substance Abuse and Mental Health Services Administration regarding implementation of evidence-based programs. The New York State effort largely follows these recommendations, including (1) close collaboration between OMH officials, local facility personnel, and cognitive remediation experts on implementation choices, methods, and resources; (2) a standardized and sustainable staff training program that teaches evidence-based practices to busy clinicians and supports treatment fidelity; (3) program evaluation activities that support provision of high-quality care; and (4) treatment adaptations that meet the needs of a culturally diverse and multilingual SMI population. Several noteworthy features of the project include the following:

Stages of Implementation and Best Practices to Promote Adoption, Installation, and Continuity of Evidence-Based Programs

Note : Stages of implementation are based on the National Implementation Research Network’s synthesis of implementation research and practice studies. 67 Recommended actions are from guidance provided by the Substance Abuse and Mental Health Services Administration regarding implementation of evidence-based programs. 68 .

Cognitive remediation experts worked closely with OMH leaders and local clinic administrators to operationalize a public psychiatry model of cognitive health and to solve pragmatic questions about staffing models, clinical workflows, information technology needs, and billing practices.

Cognitive remediation services were implemented in a staggered manner, starting with outpatient clinics serving adults with SMI diagnoses 61 and later expanded to Coordinated Specialty Care (CSC) programs for first-episode psychosis. 62 , 63 The latter effort adopted recovery values, organizational principles, and implementation methods pioneered in the adult SMI programs, but modified them to address the needs and perspectives of younger service users. 64

Workforce development programs were created to build broad and enduring support for cognitive remediation interventions. All clinical and support staff received education about cognitive health and recovery; selected clinicians received targeted training and ongoing supervision in cognitive assessment, treatment planning, and intervention practices. Train-the-trainer classes were established to maintain a pool of competent instructors to teach these skills to new clinicians, as needed.

Clinicians collect program evaluation data as part of routine care; supervisors use these data to monitor treatment fidelity and troubleshoot implementation problems in real-time. Pragmatic measures of service utilization, dropout rates, and participant satisfaction confirm the fidelity, acceptability, and perceived effectiveness of cognitive remediation in state-operated clinics, 65 but also identify areas for further improvement. 66

The New York State implementation experiment responds to several research priorities outlined in the recent White House Report. 59 The initiative successfully expands the cognitive remediation workforce to include psychologists, nurses, physicians, social workers, and mental health counselors who work in community treatment settings. The public psychiatry model 61 assures that almost all persons served in state-operated clinics for adults, and CSC programs for youth, are eligible to receive cognitive health services. Integrating cognitive remediation into existing multidisciplinary rehabilitation programs furthers OMH’s commitment to person-centered, recovery-oriented treatment that fosters patients’ independence and community engagement. Innovative methods for training clinicians, tracking their performance, and maintaining treatment fidelity are sustaining the implementation of high-quality interventions over time. Finally, the extension of cognitive health services into CSC programs illustrates the importance of involving end-users, eg, CSC service providers 62 and persons with lived experience, 64 in developing interventions that are feasible to implement and responsive to the needs and preferences of the target population.

While these accomplishments are a clear step forward, further research in public sector settings is needed to (1) optimize the delivery of cognitive interventions (eg, increase referrals, participant enrollment, and service utilization); (2) eliminate potential inequalities in access, quality, or effectiveness of services for populations with health disparities 69 ; (3) evaluate the impact of cognitive interventions on objective measures of patients’ social, educational, and vocational functioning; and (4) determine the cost-effectiveness of combining cognitive remediation programs with traditional psychiatric rehabilitation services. These and similar practice-oriented research questions could be explored within a learning health care framework, where data collected as part of routine care are used to study the implementation, adaptation, and effectiveness of evidence-based interventions in public health clinics. 70 Such an approach ensures that research findings are directly relevant to representative sets of patients, clinicians, and health care system administrators, while clinical practice benefits from continuous data-driven improvement. 71

Throughout 2024, NIMH is celebrating 75 years of basic, translational, and health services research that has deepened our understanding of mental disorders and broadened the therapeutic armamentarium. Cognitive intervention research for schizophrenia has featured prominently in the Institute’s scientific portfolio, with sequential treatment development initiatives over the past 2 decades. A core set of principles guided these efforts, including convening diverse learning communities, using structured encounters to establish a common scientific framework and vocabulary for understanding complex challenges, and creating funding opportunities that encourage interdisciplinary, deployment-focused studies. Increasingly, teams that partner translational scientists, implementation researchers, and mental health shareholders, eg, service users, family members, clinicians, payers, and policymakers, are developing and testing interventions that align with conditions encountered in real-world treatment systems. This approach holds promise for speeding the introduction of evidence-based practices in these settings, thereby narrowing the typical research-to-implementation gap. 72 Going forward, science-to-service studies conducted within the learning health model will further accelerate progress toward clinically effective, continuously improving, and accessible cognitive health care for all persons with psychotic disorders.

The authors have no conflicts of interest to disclose. The views expressed in this article do not necessarily represent the views of the National Institutes of Health, the Department of Health and Human Services, or the United States Government.

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